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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 18-JAN-08 Species laboratory mouse Generation N24+F4 (22-OCT-09) Donating Investigator David Cohen, Brigham and Women's Hospital Description
Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. Protein product from the targeted gene is not detected in the liver cytosol of 8-day-old homozygous pups. The lipid content and composition of bile and lung surfactant secretions are normal in homozygous targeted mice. Plasma cholesterol and phospholipid levels are not affected in chow-fed homozygous targeted mutation mice, but there is an increase in the accumulation of small alpha-migrating high density lipoprotein (HDL) particles. Biliary concentrations of phospholipids, cholesterol, and bile salts are reduced in homozygous mutants as compared to wildtype mice when fed a high fat, high cholesterol, cholate-containing lithogenic diet. There is a greater hepatic accumulation of phospholipid and cholesterol in the targeted mutant animals. On the high fat diet, HDL particles are of normal size, but plasma cholesterol and phospholipid concentrations are increased compared to wildtype mice. This strain represents a model that may be useful in studies of lipid metabolism.Development
A targeting vector containing a neomycin resistance gene was used to replace exons C and D by homologous recombination. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. The resultant strain has been backcrossed approximately twenty times to C57BL/6 by the donating laboratory.
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
View Strains carrying other alleles of Pctp (3 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Pctptm1Bor/Pctptm1Bor
B6.129P2-Pctptm1Bor
- cellular phenotype
- increased apoptosis (MGI Ref ID J:115284)
- macrophages loaded with free (unesterified) cholesterol (FC) show significantly more apoptotic cell death and total cell death compared to FC-loaded wild-type macrophages
- immune system phenotype
- abnormal macrophage physiology (MGI Ref ID J:115284)
- macrophages loaded with cholesteryl esters show impaired apoAI-mediated efflux of phospholipids and cholesterol compared to wild-type macrophages
- macrophages loaded with free (unesterified) cholesterol (FC) show significantly more apoptotic cell death and total cell death compared to FC-loaded wild-type macrophages
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Pctptm1Bor/Pctptm1Bor
involves: 129P2/OlaHsd * FVB
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:57946)
- mice do not exhibit defects in lipid metabolism, liver function or lung surfactant production
Pctptm1Bor/Pctptm1Bor
involves: 129P2/OlaHsd * C57BL/6J
- liver/biliary system phenotype
- abnormal bile canaliculus morphology (MGI Ref ID J:115285)
- in mutant livers, bile canaliculi show extensive branching at membrane surface
- abnormal gall bladder physiology (MGI Ref ID J:115285)
- occlusion of gall bladder with mucin occurs at 7 days on a lithogenic diet compared to 18 hours on the FVB/NJ background
- abnormal bile composition (MGI Ref ID J:115285)
- phospholipids in bile of mice on a chow diet are 1.3 fold higher than littermates
- on a lithogenic diet, after 7 days, mice have 1.3 fold lower phospholipid levels in bile
- on a lithogenic diet, after 7 days, mice have 1.3 fold lower biliary cholesterol levels in bile compared to wild-type littermates
- gallstones (MGI Ref ID J:115285)
- on a lithogenic diet, abundant liquid and solid cholesterol crystals that precede formation of macroscopic cholesterol gallstones are observed after 9 days
- homeostasis/metabolism phenotype
- abnormal bile salt level (MGI Ref ID J:115285)
- on a lithogenic diet, TUDC concentration increases in mutants and controls, but remain higher in mutants; TC remains unchanged in mutants but increases in wild-type
- relative concentration of tauromuricholate (TMC) is reduced and tauroursdeoxycholate (TUDC) and taurocholate (TC) concentrations are increased compared to control
- bile salt concentrations are 1.3 fold lower than controls on lithogenic diets compared to mutants on the FVB/NJ background
- abnormal phospholipid level (MGI Ref ID J:115285)
- phospholipids in bile of mice on a chow diet are 1.3 fold higher than littermates
- on a lithogenic diet, after 7 days, mice have 1.3 fold lower phospholipid levels in bile
Pctptm1Bor/Pctptm1Bor
involves: 129P2/OlaHsd * FVB/NJ
- liver/biliary system phenotype
- abnormal bile canaliculus morphology (MGI Ref ID J:115285)
- in mutant livers, bile canaliculi show extensive branching at membrane surface
- bile canaliculi and junctional complexes appear more tortuous
- abnormal gall bladder physiology (MGI Ref ID J:115285)
- occlusion of gall bladder with mucin occurs at 18 hours on a lithogenic diet
- occlusion occurs much more quickly than on the C57BL/6J background
- abnormal bile secretion (MGI Ref ID J:115285)
- bile flow rate is reduced by ~35% after 30 minutes in mutants on a regular chow diet
- homeostasis/metabolism phenotype
- abnormal bile salt level (MGI Ref ID J:115285)
- bile salt concentrations are 4.3 fold higher than controls on regular chow diets
- there is marked increase in bile salt secretion on chow diet
- on lithogenic diet, concentration decreases; in wild-type, concentrations increase such that both genotypes have similar bile salt concentrations
- on a chow diet, TC concentration is higher than controls, while other bile salt concentrations are reduced; on a lithogenic diet, percentage of TUDC is higher in mutants, but other types are similar in both mutants and controls
- decreased cholesterol level (MGI Ref ID J:115285)
- on a lithogenic diet, biliary cholesterol levels decrease, but levels increase in wild-type
- increased cholesterol level (MGI Ref ID J:115285)
- in chow-fed mice, biliary cholesterol levels are 5.9 fold higher than in controls
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Metabolism Research
Lipid Metabolism
| Allele Symbol | Pctptm1Bor | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Piet Borst | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Pc-tp -; Pctp-; | ||
| Mutation Made By | Michele Wu, Brigham and Women's Hospital | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Pctp, phosphatidylcholine transfer protein | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | PC-TP; STARD2; | ||
| Molecular Note | A neomycin selection gene replaced exons C and D by homologous recombination. Western blot analysis demonstrated that no detectable protein product was made in the cytosol of cells derived from homozygous mice. [MGI Ref ID J:57946] | ||
Genotyping Protocols
Pctptm1Bor, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
van Helvoort A; de Brouwer A; Ottenhoff R; Brouwers JF; Wijnholds J; Beijnen JH; Rijneveld A; van der Poll T; van der Valk MA; Majoor D; Voorhout W; Wirtz KW; Elferink RP; Borst P. 1999. Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces. Proc Natl Acad Sci U S A 96(20):11501-6. [PubMed: 10500206] [MGI Ref ID J:57946]
Pctptm1Bor relatedBaez JM; Tabas I; Cohen DE. 2005. Decreased lipid efflux and increased susceptibility to cholesterol-induced apoptosis in macrophages lacking phosphatidylcholine transfer protein. Biochem J 388(Pt 1):57-63. [PubMed: 15628972] [MGI Ref ID J:115284]
Scapa EF; Pocai A; Wu MK; Gutierrez-Juarez R; Glenz L; Kanno K; Li H; Biddinger S; Jelicks LA; Rossetti L; Cohen DE. 2008. Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2. FASEB J 22(7):2579-90. [PubMed: 18347010] [MGI Ref ID J:138012]
Wang WJ; Baez JM; Maurer R; Dansky HM; Cohen DE. 2006. Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice. J Lipid Res 47(11):2400-7. [PubMed: 16940277] [MGI Ref ID J:147028]
Wu MK; Cohen DE. 2005. Altered hepatic cholesterol metabolism compensates for disruption of phosphatidylcholine transfer protein in mice. Am J Physiol Gastrointest Liver Physiol 289(3):G456-61. [PubMed: 15845870] [MGI Ref ID J:101230]
Wu MK; Cohen DE. 2005. Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins. Am J Physiol Gastrointest Liver Physiol 289(6):G1067-74. [PubMed: 16099870] [MGI Ref ID J:104778]
Wu MK; Hyogo H; Yadav SK; Novikoff PM; Cohen DE. 2005. Impaired response of biliary lipid secretion to a lithogenic diet in phosphatidylcholine transfer protein-deficient mice. J Lipid Res 46(3):422-31. [PubMed: 15576839] [MGI Ref ID J:115285]
Animal Health Reports
Room Number AX11
Colony Maintenance
Mating System Homozygote x Homozygote (Female x Male) 18-JAN-08 Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $171.30 Female or Male Homozygous for Pctptm1Bor
Pairs /Price (US dollars $) Pair Genotype $342.60 Homozygous for Pctptm1Bor x Homozygous for Pctptm1Bor
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $222.70 Female or Male Homozygous for Pctptm1Bor
Pairs /Price (US dollars $) Pair Genotype $445.40 Homozygous for Pctptm1Bor x Homozygous for Pctptm1Bor
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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